Survival in esophageal cancer did not improve with the addition of cetuximab (Erbitux) to conventional chemoradiation, results of a randomized trial showed.

Overall survival at 12 months was 64% with cetuximab and 65% without, and 44% versus 42% at 24 months. Results were similar for patients with adenocarcinoma or squamous cell carcinoma, investigators from the Radiation Therapy Oncology Group (RTOG) reported at the European Society of Medical Oncology World Congress on Gastrointestinal Cancer in Barcelona.

Patients with T1N1M0 to any T/NM1a disease and planned nonoperative management received paclitaxel-cisplatin chemoradiation and were randomized to cetuximab or no additional therapy. The primary endpoint was overall survival.

The trial had an accrual goal of 420 patients. Accrual of patients with adenocarcinoma ended after an interim analysis suggested patients would not benefit from the addition of cetuximab. All patient enrollment stopped when results of a trial with a design similar to that of RTOG 0436 also showed no beneficial effect of the monoclonal antibody when added to chemoradiation.

The updated analysis included 328 patients. In addition to the lack of survival difference between treatment arms, clinical complete-response rates did not differ (56% with cetuximab, 59% without), reported David Ilson, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City.

The results did confirm a survival advantage for patients who attain a complete response. For the overall study population, complete response was associated with 79% survival at 12 months and 58% at 24 months. Corresponding values for patients with residual disease were 53% and 30% (P<0.0001).

New Standard Tx for Metastatic Colon Cancer

Two different antibodies had a similar impact on survival when added to chemotherapy for patients with KRAS-wild type metastatic colorectal cancer, investigators reported.

Combining cetuximab (Erbitux) or bevacizumab (Avastin) with conventional chemotherapy resulted in a median overall survival (OS) of 29 to 30 months. Either drug "is appropriate in first line," Alan Venook, MD, of the University of California San Francisco, and colleagues concluded.

"Overall survival of 29-plus months represents a new standard for KRAS wild-type colorectal cancer and confirms progress in metastatic colorectal cancer," they added.

Venook reported findings from the CALBG/SWOG 80405 intergroup trial that compared outcomes with the two monoclonal antibodies in patients with untreated, KRAS wild-type metastatic colorectal cancer. All patients received either FOLFOX (oxaliplatin, fluorouracil, folinic acid) or FOLFIRI (folinic acid, fluorouracil, irinotecan) and were randomized to cetuximab or bevacizumab. Treatment continued until progression, death, unacceptable toxicity, or curative surgery. The primary endpoint was OS.

The trial accrued 3,058 patients, 2,334 of whom had KRAS wild-type tumors and formed the basis for the randomized trial. The final analysis comprised data for 1,134 patients.

The trial ended when a 10th interim data analysis that showed little chance of demonstrating a significant difference between the treatment groups. After a median follow-up of 40 months, the results showed a median OS of 29.04 months with bevacizumab-chemotherapy and 29.93 months with cetuximab. Progression-free survival (PFS) also did not differ between groups: 10.54 versus 10.45 months with bevacizumab and cetuximab, respectively.

Additional subgroup and molecular analyses might identify other groups of patients that benefit more or less from one antibody or the other, the authors concluded.

"There was no meaningful difference in outcome between treatment arms," Venook said in a statement. "In both arms, patients lived closed to 30 months. About 10% of patients lived more than 5 years. Overall, patients did much better than anticipated and it was indifferent to the type of treatment."

Novel Agent Extends OS

Patients with treatment-refractory metastatic colorectal cancer lived about 2 months longer when the received the investigational agent TAS-102. Median PFS improved by a modest 0.3 months. Both differences attained statistical significance, as did disease control rate.

"About 50% of patients with colorectal cancer develop metastases, and eventually many of them do not respond to standard therapy," Takayuki Yoshino, MD, of the National Cancer Center Hospital East in Chiba, Japan, said in a statement. "The study shows that TAS-102 improves overall survival in these patients compared to placebo. I believe that this agent will become one of the standards of care in the refractory setting of metastatic colorectal cancer in Japan and worldwide."

The drug consists of the novel nucleoside trifluridine and the thymidine phosphorylase inhibitor tipiracil hydrochloride, which prevents degradation of the active agent. Yoshino reported data from an international phase III randomized trial. Investigators in 13 countries enrolled patients and randomized them 2:1 to TAS-102 or placebo. All patients received best supportive care. The primary endpoint was OS. Secondary endpoints included PFS, overall response rate, disease control rate, and safety.

When the trial ended, patients in the TAS-102 arm had a median OS of 7.1 months versus 5.3 months in the placebo group representing a 32% reduction in the hazard (P<0.0001). Median PFS was 2.0 months with TAS-102 and 1.7 months with placebo, representing a 48% reduction in the hazard ratio (P<0.0001). Response did not differ between the arms (1.6% with TAS-102 versus 0.4% with placebo). Patients in the TAS-102 group did have a statistically significant advantage with respect to disease control rate (overall response plus stable disease), which was 44.0% with the investigational agent and 16.3% without (P<0.0001).

Neutropenia (34.9%), leukopenia (12.8%), and anemia (16.5%) were the most common adverse events that were grade 3 or worse severity.

OS in Pancreatic Cancer

Median OS increased by about 2 months in patients with gemcitabine-refractory pancreatic cancer treated with a novel liposomal formulation of irinotecan, results of a phase III trial showed.

Patients who received fluorouracil (5-FU) and leucovorin (folinic acid) had a median survival of 4.2 months, which increased to 6.1 months in patients who received the two agents plus MM-398, which is irinotecan encapsulated in nanoliposomes. Median PFS doubled from 1.5 months without MM-398 to 3.1 months with it, as reported by Andrea Wang-Gillam, MD, PhD, of Washington University in St. Louis, on behalf of investigators at 100 sites around the world.

Data analysis included 417 patients, who were randomized to 5-FU and leucovorin, with or without MM-398, or to a third arm of MM-398 alone. The trial had a primary endpoint of OS, comparing both MM-398 arms to the control group treated with 5-FU and leucovorin.

In addition to OS and PFS, time to treatment failure and objective response rate were higher with MM-398 plus 5-FU and leucovorin versus 5-FU and leucovorin alone. Patients treated with MM-398 alone had outcomes that did not differ significantly from those of the control group.

Febrile neutropenia occurred in 1.7%, 41%, and 0% of patients in the three groups, and sepsis in 3.4%, 2.0%, and 0.7%.

"This trial has important clinical implications in a difficult setting, because we will be able to add the new drug to standard treatment and increase activity and efficacy," conference spokesperson Roberto Labianca, MD, of Ospedale Giovanni XXII in Bergamo, Italy, said in a statement.

"The trial demonstrated that nanoliposomal irinotecan plus 5-FU/leucovorin was an effective second-line therapy in metastatic pancreatic cancer. Future trials should evaluate this combination as first-line treatment and in locally advanced pancreatic cancer."

CALGB/SWOG 80405 was supported by the National Cancer Institute, Cancer and Leukemia Group B, and the Southwest Oncology Group.

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